This invention relates to methods and apparatus for improving the accuracy of measurements made with instruments of the type described in, for example, U.S. Patents: U.S. Pat. Nos. 5,243,516; 5,288,636; 5,352,351; 5,385,846; and 5,508,171. The invention is disclosed in the context of such an instrument, but is believed to be useful in other instruments of this general type as well.
There are a number of instruments for the determination of the concentrations of biologically significant components of bodily fluids, such as, for example, the glucose concentration of blood. There are, for example, the instruments described in U.S. Patents: U.S. Pat. Nos. 3,770,607; 3,838,033; 3,902,970; 3,925,183; 3,937,615; 4,005,002; 4,040,908; 4,086,631; 4,123,701; 4,127,448; 4,214,968; 4,217,196; 4,224,125; 4,225,410; 4,230,537; 4,260,680; 4,263,343; 4,265,250; 4,273,134; 4,301,412; 4,303,887; 4,366,033; 4,407,959; 4,413,628; 4,420,564; 4,431,004; 4,436,094; 4,440,175; 4,477,314; 4,477,575; 4,499,423; 4,517,291; 4,654,197; 4,671,288; 4,679,562; 4,682,602; 4,703,756; 4,711,245; 4,734,184; 4,750,496; 4,759,828; 4,789,804; 4,795,542; 4,805,624; 4,816,224; 4,820,399; 4,897,162; 4,897,173; 4,919,770; 4,927,516; 4,935,106; 4,938,860; 4,940,945; 4,970,145; 4,975,647; 4,999,582; 4,999,632; 5,108,564; 5,128,015; 5,243,516; 5,269,891; 5,288,636; 5,312,762; 5,352,351; 5,385,846; 5,395,504; 5,469,846; 5,508,171; 5,508,203; and 5,509,410: German Patent Specification 3,228,542: European Patent Specifications: 206,218; 230,472; 241,309; 255,291; and, 471,986: and, Japanese Published Patent Applications JP 63-128,252 and 63-111,453. There are also the methods and apparatus described in: Talbott, et al, xe2x80x9cA New Microchemical Approach to Amperometric Analysis,xe2x80x9d Microchemical Journal, Vol. 37, pp. 5-12 (1988); Morris, et al, xe2x80x9cAn Electrochemical Capillary Fill Device for the Analysis of Glucose Incorporating Glucose Oxidase and Ruthenium (III) Hexamine as Mediator, Electroanalysis,xe2x80x9d Vol. 4, pp. 1-9 (1992); Cass, et al, xe2x80x9cFerrocene-Mediated Enzyme Electrode for Amperometric Determination of Glucose,xe2x80x9d Anal. Chem., Vol. 56, pp. 667-671 (1984); Zhao, xe2x80x9cContributions of Suspending Medium to Electrical Impedance of Blood,xe2x80x9d Biochimica et Biophysica Acta, Vol. 1201, pp. 179-185 (1994); Zhao, xe2x80x9cElectrical Impedance and Haematocrit of Human Blood with Various Anticoagulants,xe2x80x9d Physiol. Meas., Vol. 14, pp. 299-307 (1993); Muller, et al., xe2x80x9cInfluence of Hematocrit and Platelet Count on Impedance and Reactivity of Whole Blood for Electrical Aggregometry,xe2x80x9cJournal of Pharmacological and Toxicological Methods, Vol. 34, pp. 17-22 (1995); Preidel, et al, xe2x80x9d In Vitro Measurements with Electrocatalytic Glucose Sensor in Blood,xe2x80x9d Biomed. Biochim. Acta, Vol. 48, pp. 897-903 (1989); Preidel, et al, xe2x80x9cGlucose Measurements by Electrocatalytic Sensor in the Extracorporeal Blood Circulation of a Sheep,xe2x80x9d Sensors and Actuators B, Vol. 2, pp.257-263 (1990); Saeger, et al, xe2x80x9cInfluence of Urea on the Glucose Measurement by Electrocatalytic Sensor in the Extracorporeal Blood Circulation of a Sheep,xe2x80x9d Biomed. Biochim. Acta, Vol. 50, pp. 885-891 (1991); Kasapbasioglu, et al, xe2x80x9cAn Impedance Based Ultra-Thin Platinum Island Film Glucose Sensor,xe2x80x9d Sensors and Actuators B, Vol. 13-14, pp. 749-751 (1993); Beyer, et al, xe2x80x9cDevelopment and Application of a New Enzyme Sensor Type Based on the EIS-Capacitance Structure for Bioprocess Control,xe2x80x9d Biosensors and Bioelectronics, Vol. 9, pp. 17-21 (1994); Mohri, et al, xe2x80x9cCharacteristic Response of Electrochemical Nonlinearity to Taste Compounds with a Gold Electrode Modified with 4-Aminobenzenethiol,xe2x80x9d Bull. Chem. Soc. Jpn., Vol. 66, pp. 1328-1332 (1993); Cardosi, et al, xe2x80x9cThe Realization of Electron Transfer from Biological Molecules to Electrodes,xe2x80x9d Biosensors Fundamentals and Applications, chapt. 15 (Turner, et al, eds., Oxford University Press, 1987); Mell, et al, xe2x80x9cAmperometric Response Enhancement of the Immobilized Glucose Oxidase Enzyme Electrode,xe2x80x9d Analytical Chemistry, Vol. 48, pp. 1597-1601 (Sept. 1976); Mell, et al, xe2x80x9cA Model for the Amperometric Enzyme Electrode Obtained Through Digital Simulation and Applied to the Immobilized Glucose Oxidase System,xe2x80x9d Analytical Chemistry, Vol. 47, pp. 299-307 (Feb. 1975); Myland, et al, xe2x80x9cMembrane-Covered Oxygen Sensors: An Exact Treatment of the Switch-on Transient,xe2x80x9d Journal of the Electrochemical Society, Vol. 131, pp. 1815-1823 (Aug. 1984); Bradley, et al, xe2x80x9cKinetic Analysis of Enzyme Electrode Response,xe2x80x9d Anal. Chem., Vol. 56, pp. 664-667 (1984); Koichi,xe2x80x9cMeasurements of Current-Potential Curves, 6, Cottrell Equation and its Analogs. What Can We Know from Chronoamperometry?xe2x80x9d Denki Kagaku oyobi Kogyo Butsuri Kagaku, Vol. 54, no.6, pp. 471-5 (1986); Williams, et al, xe2x80x9cElectrochemical-Enzymatic Analysis of Blood Glucose and Lactate,xe2x80x9d Analytical Chemistry, Vol. 42, no. 1, pp. 118-121 (Jan. 1970); and, Gebhardt, et al, xe2x80x9cElectrocatalytic Glucose Sensor,xe2x80x9d Siemens Forsch.-u. Entwickl.-Ber. Bd., Vol. 12, pp.91-95 (1983). This listing is not intended as a representation that a complete search of all relevant prior art has been conducted, or that no better references than those listed exist. Nor should any such representation be inferred.
According to one aspect of the invention, an apparatus for determining the concentration of a medically significant component of a biological fluid comprises a cell for receiving a sample of the fluid. The cell supports a chemistry which reacts with the medically significant component and first and second terminals across which the reaction of the chemistry with the medically significant component can be assessed. The apparatus further comprises an instrument having first and second terminals complementary to the first and second terminals, respectively, of the cell. Placement of the first and second terminals of the cell in contact with the first and second terminals, respectively, of the instrument permits the instrument to assess the reaction. The instrument includes an assessment controller for applying across the first and second terminals of the instrument a first signal, determining a first response of the cell to the first signal, and determining based upon the first response whether to proceed with the determination of the concentration of the medically significant component of the biological fluid.
According to another aspect of the invention, an apparatus for determining the concentration of a medically significant component of a biological fluid comprises a cell for receiving a sample of the fluid. The cell supports a chemistry which reacts with the medically significant component and first and second terminals across which the reaction of the chemistry with the medically significant component can be assessed. The apparatus further comprises an instrument having first and second terminals complementary to the first and second terminals, respectively, of the cell. Placement of the first and second terminals of the cell in contact with the first and second terminals, respectively, of the instrument permits the instrument to assess the reaction. The instrument includes an assessment controller for applying across the first and second terminals of the instrument a first signal, determining a first correction value in response of the cell to the first signal, assessing the reaction of the medically significant component with the chemistry and combining the correction value with the result of the reaction assessment to produce an indication of the concentration of the medically significant component in the sample.
According to another aspect of the invention, an apparatus for determining the concentration of a medically significant component of a biological fluid comprises a cell for receiving a sample of the fluid. The cell supports a chemistry which reacts with the medically significant component and first and second terminals across which the reaction of the chemistry with the medically significant component can be assessed. The apparatus further comprises an instrument having first and second terminals complementary to the first and second terminals, respectively, of the cell. Placement of the first and second terminals of the cell in contact with the first and second terminals, respectively, of the instrument permits the instrument to assess the reaction. The instrument includes an assessment controller for applying across the first and second terminals of the instrument a first signal, determining the identity of the sample in response of the cell to the first signal, and producing an indication of the identity of the sample.
According to yet another aspect of the invention, a method for determining the concentration of a medically significant component of a biological fluid comprises providing a cell for receiving a sample of the fluid, and providing on the cell a chemistry which reacts with the medically significant component and first and second terminals across which the reaction of the chemistry with the medically significant component can be assessed. The method further comprises providing an instrument having first and second terminals complementary to the first and second terminals, respectively, of the cell. Placement of the first and second terminals of the cell in contact with the first and second terminals, respectively, of the instrument permits the instrument to assess the reaction. The method further comprises providing in the instrument an assessment controller, causing the assessment controller to apply across the first and second terminals of the instrument a first signal, causing the assessment controller to determine a first response of the cell to the first signal, and causing the assessment controller to determine, based upon the first response, whether to proceed with the determination of the concentration of the medically significant component of the biological fluid.
According to a further aspect of the invention, a method for determining the concentration of a medically significant component of a biological fluid comprises providing a cell for receiving a sample of the fluid, and providing on the cell a chemistry which reacts with the medically significant component and first and second terminals across which the reaction of the chemistry with the medically significant component can be assessed. The method further comprises providing an instrument having first and second terminals complementary to the first and second terminals, respectively, of the cell. Placement of the first and second terminals of the cell in contact with the first and second terminals, respectively, of the instrument permits the instrument to assess the reaction. The method further comprises providing in the instrument an assessment controller, causing the assessment controller to apply across the first and second terminals of the instrument a first signal, to determine a first correction value in response to the first signal, to assess the reaction of the medically significant component with the chemistry, and to combine the correction value with the result of the reaction assessment to produce an indication of the concentration of the medically significant component in the sample.
According to a further aspect of the invention, a method for determining the concentration of a medically significant component of a biological fluid comprises providing a cell for receiving a sample of the fluid, and providing on the cell a chemistry which reacts with the medically significant component and first and second terminals across which the reaction of the chemistry with the medically significant component can be assessed. The method further comprises providing an instrument having first and second terminals complementary to the first and second terminals, respectively, of the cell. Placement of the first and second terminals of the cell in contact with the first and second terminals, respectively, of the instrument permits the instrument to assess the reaction. The method further comprises providing in the instrument an assessment controller for applying across the first and second terminals of the instrument a first signal, determining the identity of the sample in response of the cell to the first signal, and producing an indication of the identity of the sample.
Illustratively, the first signal comprises a signal having an AC component. Further illustratively, the first signal comprises an AC signal.
Additionally illustratively, the method of, and apparatus for, determining the correction value, the method of, and apparatus for, determining the identity of the sample, and the method of, and apparatus for, determining whether to proceed with the determination of the concentration of the medically significant component of the biological fluid comprise the step of, and apparatus for, determining the impedance across terminals of the cell.